Chromatography involves the flow of a mobile phase over a stationary phase. Liquid chromatography is used for soluble substances, and gas chromatography for volatile substances. As the mobile phase moves past the stationary phase, repeated adsorption and desorption of the solute occurs at a rate determined chiefly by its distribution ratio between the two phases. If the ratio is large enough, the components of the mixture will move at different rates, producing a series of bands or chromatographs by which their identity can be determined. The analysis of many biological samples is commonly performed using a chromatographic technique known as high performance liquid chromatography (HPLC). Typical packing materials employed in HPLC and other chromatographic columns of various lengths include silica gel, alumina, glass beads, polystyrene gel and ion exchange resins. Separation of materials in a sample is effected by the affinity of a sample component or isolate towards the packing material. For example, hydrophobic substances can generally be separated by using hydrophobic octadecylsilane columns or another alkyl-bonded silica column. However, one problem, encountered in the analysis of biological samples with such packing material, is that proteins in many biological samples denature on the hydrophobic surfaces of packing material, adsorb onto the support particulates and accumulate inside the chromatographic column to eventually damage the column. One approach to overcome this problem has been to pretreat the biological sample, such as, for example, by protein precipitation followed by organic extraction, or the removal of proteins and analities on large particulate silica bonded materials, either off-line or as a precolumn. Various solid-phase extraction techniques for sample preparation are reviewed in Tippins, American Laboratory, p. 107 (February 1987). These techniques are undesirable, however, because of the additional sample processing and time required.
An alternative approach for avoiding protein denaturation in HPLC analysis of biological samples has been the use of silica packing materials wherein the hydrophobic partitioning phase is confined exclusively to the internal particulate region of a porous silica support, while keeping the external surface of the support hydrophilic and non-adsorptive to proteins. Such chromatographic support material is also known as an internal surface reversed-phase (ISRP) support. It has been known to prepare such ISRP packings using an elaborate procedure. In the conventional ISRP preparation procedure, small-pore-diameter silica is first modified with a glycerylpropyl bonded phase. Polypeptides with hydrophobic moieties which are susceptible to enzyme cleavage are then covalently bound to the glycerylpropyl phase. The derivitized packing is then treated with enzymes to remove the hydrophobic species from only the external surface by selecting enzymes which are too large to enter the internal surface region. Such ISRP supports are described, for example, in Hagestam et al, Analytical Chemistry, vol. 57, pp. 1757-1763 (1985); Pinkerton et al, BioChromatography, vol. 1, pp. 96-105 (1986); and Pinkerton, American Laboratory, pp. 70-76 (April 1988). Pinkerton ISRP columns are commercially available from Regis Chemical Co. ISRP supports having a phase bonded with propylamine-coupled lecithin-imidazolide are described in Pidgeon, Chemical & Engineering News, pp. 23-24 Dec. 12, 1988).
The use of particulate materials similar to chromatographic column supports is common in other applications as well. For example, the use as catalysts of aerogels containing minor impurities is well known. Such catalysts have been used, for example, in the conversion by nitric oxide of paraffins, olefins, and alkylaromatics into nitriles. Such catalysts are typically activated by exposing the catalyst to oxygen or an oxygen-containing gas at extremely elevated temperatures, such as, for example, 400.degree. C. and above for 24-48 hours, or about the time required for spinel formation. Such catalysts have been investigated in, for example, Rahman et al, Applied Catalysis, Vol. 36, pp. 209-220 (1988). However, exposure of the aerogel catalysts to high temperature during activation can have an undesired effect on other properties of the catalyst, such as the textural and structural aspects thereof, and has given rise to attempts to avoid high temperature activation. From U.S. Pat. No. 3,963,646 to Teichner et al., for example, it is known to form hydrogenation or controlled oxidation catalysts by coprecipitation of mixtures of hydrolyzable salts of a transition metal and a refractory metal oxide in a non-aqueous solvent with the simultaneous addition of a stoichiometric amount of water, followed by drying of the coprecipitate under hypercritical conditions.
Membranes have a significant role in industrial processing, especially in the biotechnology, industrial gas separation and drug delivery device areas. The preparation of membranes having a symmetrical physical and surface-chemical properties has been described, for example, in Haggin, Chemical and Engineering News, p. 25-32 Jul. 11, 1988). Such membranes have been used in membrane reactors which combine catalytic reaction with product separation. Successful membrane reactors require surface chemistry which varies with location in the cross-section of the membrane. However, the layering of different materials to form such composite membranes involves a difficult fabrication and results in the deposition of inherently thick layers.
Various techniques are known for the plasma activated chemical vapor deposition onto a substrate. For example, from U.S. Pat. No. 3,826,226 to Clark, it is known to deposit a controlled thickness metallic coating such as gold, silver, copper or aluminum onto small particles such as glass spheres using a drop tower for gravity feed of the particles through a vapor coating chamber. An ion beam which is disposed laterally offset from and optically shielded with respect to the drop tower provides a vaporized coating medium in the coating chamber.
From U.S. Pat. No. 4,268,711 to Gurev, it is known to deposit a thin film onto a substrate from a vapor employing a contained plasma source wherein a chemical reaction, such as between aluminum trichloride, silane and oxygen to produce vapors of silicon dioxide and aluminum oxide, takes place within the plasma and/or at the substrate surface being coated which is maintained at a low temperature.
From U.S. Pat. No. 4,583,492 to Cowher et al., it is known to use a plasma-enhanced vapor deposition reactor to coat a substrate with amorphous silica wherein the reactor is configured so as to avoid plugging of the vacuum pump associated with the reactor. Similar equipment and techniques are described, for example, in U.S. Pat. No. 4,608,063 to Kurokawa and U.S. Pat. No. 4,686,113 to Delfino et al.
In U.S. Pat. No. 4,362,632 to Jacob there is described a gas discharge apparatus wherein a perforated metallic cylinder is disposed concentrically within a reaction chamber so that activated gas introduced thereto provides very uniform distribution of gaseous excited species throughout the entire material processing volume within the cylinder to obtain very uniform chemical conversions therein.
U.S. Pat. No. 3,702,973 to Daugherty et al. teaches an apparatus for making ozone or other excited species which uses a laser to excite a gas flow, such as nitrogen, carbon dioxide or helium. In this apparatus, consideration is given to maintaining the plasma contained inside the electric discharge tube in a radially smooth condition by making the time required for diffusion to the surrounding walls equal to the ionization time.
U.S. Pat. No. 3,904,366 to Grasenick teaches an apparatus in which a sample material is exposed to an excited gas such as oxygen to convert the components of the substance into gaseous compounds which may be measured quantitively by an analytical method.
U.S. Pat. No. 4,756,794 to Yoder teaches an apparatus for etching the surface of a material such as diamond to remove a single atomic layer therefrom. In one embodiment described in this reference, energetic ions from an ion gun impinge on nitrogen oxide gas decomposing it into atomic oxygen and nitrogen so as to erode the surface.
A diffusion method of investigating surface recombination of hydrogen atoms and OH radicals using a sidearm reaction apparatus is described in Smith, Journal of Chemical Physics, vol. 11, pp. 110-125 (1943).